Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice

• Published in: Archives of toxicology 2017, Vol.91 (1), p.453-464
• Main Authors: Lee, Byoung-Seok, Park, Sang-Jin, Kim, Yong-Bum, Han, Ji-Seok, Jeong, Eun Ju, Son, Hwa-Young, Moon, Kyoung-Sik
• Format: Article
• Language: English
• Subjects: Administration, Oral; alpha-Chlorohydrin - administration & dosage; alpha-Chlorohydrin - toxicity; Animals; Biomedical and Life Sciences; Biomedicine; Brain - cytology; Brain - drug effects; Carcinogenicity Tests; Carcinogens; Crosses, Genetic; Environmental Health; Epididymis - cytology; Epididymis - drug effects; Female; Food; Humans; Kidney - cytology; Kidney - drug effects; Male; Mice, Inbred BALB C; Mice, Transgenic; Neurons - cytology; Neurons - drug effects; Occupational Medicine/Industrial Medicine; Organ Size - drug effects; Organ Toxicity and Mechanisms; Pharmacology/Toxicology; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Random Allocation; Rodents; Specific Pathogen-Free Organisms; Spinal Cord - cytology; Spinal Cord - drug effects; Survival Analysis; Testis - cytology; Testis - drug effects; Transgenic animals; Vacuoles - drug effects
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-016-1696-9

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 ras H2-Tg ( ras H2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female ras H2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N -methyl- N -nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most ras H2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using ras H2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.